The present invention relates to an injectable tissue graft composition and methods for its preparation and use. More particularly, the present invention is directed to injectable, non-immunogenic tissue graft compositions derived from intestinal submucosa. Upon deposition in vivo in an area of a tissue defect, the present fluidized tissue graft compositions promote growth of endogenous tissue to repair the defect.
It has been reported that compositions comprising the submucosa and the basilar portions of the tunica mucosa of the intestine of warm-blooded vertebrates can be used as tissue graft materials in sheet form. See U.S. Pat. No. 4,902,508. The preferred trilaminate sheet compositions described and claimed in that patent are characterized by excellent mechanical properties, including high compliance, a high burst pressure point, and an effective porosity index which allowed such compositions to be used beneficially for vascular graft constructs. The graft materials disclosed in that patent are also useful in tendon and ligament replacement applications. When used in such applications the preferred trilaminate graft constructs appear to serve as a matrix for the regrowth of the tissues replaced by the graft constructs. It was believed that such properties derived from the unique trilaminate sheet structures of the intestinal tissue derived graft constructs.
Surprisingly, it has been discovered that intestinal submucosa can be fluidized by comminuting and/or protease digestion, without loss of its apparent biotropic properties, for use in less invasive methods of administration (e.g., injection or topical) to host tissues in need of repair.
According to the present invention, an injectable, non-immunogenic tissue graft composition is provided. In one embodiment the composition comprises comminuted large or small intestinal submucosa, preferably in an aqueous suspension. In another aspect of the invention, there is provided a composition comprising protease-digested intestinal submucosa.
The fluidized composition is used advantageously in a method for inducing formation of endogenous tissue including bone and soft tissues such as muscle and connective tissues in a warm-blooded vertebrate. The method comprises the step of injecting into the vertebrate a composition comprising a suspension of comminuted intestinal submucosa or a protease digest thereof in an amount effective to induce endogenous tissue growth in the locale of the injected fluidized tissue graft composition. Endogenous connective tissues induced to grow in accordance with this invention include collagen, elastin and muscle.
In another more specific aspect of the present invention, a method is provided for augmenting sphincter function in a warm-blooded mammal, the method comprising the step of injecting into tissue forming said sphincter an effective amount of a tissue graft composition comprising an aqueous suspension of comminuted intestinal submucosa. In yet a further aspect of the present invention, a method is provided for augmenting sphincter function in which the injectable composition comprises protease digested intestinal submucosa.
The injectable or "fluidized" compositions in accordance with the present invention can be used in a wide variety of tissue repair or tissue reconstruction applications. They can be used alone or in combination with the graft material described in U.S. Pat. No. 4,902,308. For example, the compositions of the present invention can be used for surgical reconstruction of a collagenous meniscus at the interface of articulating bones. In such reconstruction a sheet of a first tissue graft composition, preferably itself comprising intestinal submucosa of a warm-blooded vertebrate, is formed into a sealed pouch and filled with a fluidized tissue graft composition of this invention.
Additional objects, features, and advantages of the invention will become apparent to those skilled in the art upon consideration of the following detailed description of preferred embodiments exemplifying the best mode of carrying out the invention as presently perceived.